Regulation of clinical trials with medicinal products: Where are we now? Mariantonia Serrano Castro Department of Medicines for Human Use Agencia Española de Medicamentos y Productos Sanitarios (AEMPS) CMC Strategy Forum Europe 2011 Barcelona, 21st March 2011
Basic legislation on CT Directive 2001/20/CE Parliament and Council, 4th April, Law 29/2006, 26th July, on guarantees and rational use of medicinal products and M.D. (Law on medicinal products). Royal Decree 223/2004, 6 February, clinical trials (CT) of medicinal products
CT Subject Protection Legislation objectives and scope Área de Ensayos Clínicos Transparency Risks for environment Guarantees of Quality in the Results NCAs cooperation on CT assessment and inspection
Common procedures Área de Ensayos Clínicos Legislation objectives and scope for Ethics Committee and for Competent Authority CT assessment Standard for required notifications and for CT documentation
EudraLex Volume 10 Clinical Trials http://ec.europa.eu/health/documents/eudralex/vol- 10/index_en.htm -1 P.&C. Directive + 2 Commission Directives - CT dossier for CA and for EC - Safety rules (SUSAR, DSUR) - Quality of IMP rules (including GMP) - Good Clinical Practice and inspections - Rules for publication of CT - Ethical issues for paediatric CT
www.aemps.es Clinical Investigation
www.aemps.es Área Clinical de Ensayos Investigation Clínicos Clinical Investigation with medicinal products Clinical Trials
Before During... After. EudraCT No. Protocol Plan GCP standards IMP quality standards Insurance Single opinion by EC Agreement sponsor site for every site AEMPS authorisation Ministry MARM authorisation (If CT on GMO) Significant amendments review by EC/AEMPS CT monitoring (including safety monitoring) SAE/SUSAR reporting Annual safety report (DSUR) Public registration of CT End of trial notification Results report Publication of results
Transparency EU CT application form AEMPS CT Data base National Clinical Trials register (art. 62 Law 29/2006) EudraCT (EU database on CT on IMP) EU Clinical Trials Register All paediatric CT and phase II to IV non paediatric
www.aemps.es Área Clinical de Ensayos Investigation Clínicos Office for supporting Independent Clinical Investigation
Where are we now?
Clinical trials authorised in Spain 800 700 600 636 588 665 675 707 643 500 400 300 200 100 0 2005 2006 2007 2008 2009 2010 Subdirección n General de Medicamentos de Uso Humano
Clinical trial applications in the EU 5300 3969 4334 5028 4618 4491 4153 0 2005 2006 2007 2008 2009 2010 Number of CT applications according to year of loading in EudraCT Source: EudraCT
Clinical Trials Facilitation Área Group de Ensayos Clínicos VHP (voluntary harmonization procedure) Simultaneous scientific assessment by the concerned Competent Authorities: CTFG-VHP For CT with 3 o more EU countries Application to the CTFG: Unique CT dossier, single e-application to CTFG, coordinated assessment, single list of questions, 60 days max. Quick official national application afterwards (authorisation <10 days since a valid application) CTFG: http://www.hma.eu/77.html
Where are we going? 1 Legislative changes 2 Operative changes
Where are we going? 1 Legislative changes
2012 new Directive Cooperation in assessing and following up applications for clinical trials Risk adapted approach to the procedural aspects of clinical trials Ensuring compliance with good clinical practice in clinical trials performed in third countries http://ec.europa.eu/health/files/clinicaltrials/concept _paper_02-2011.pdf
volume 10 Eudralex update Question & Answer (v8 March 2011) Development Safety Update Report (DSUR) Guidance on Investigational Medicinal Products (IMPs) and 'non investigational medicinal products' (NIMPs), rev.1 (March 2011) CT-3 guidance on safety and SUSAR reporting (COM Public consultation on 2010) http://ec.europa.eu/health/human-use/clinicaltrials/developments/index_en.htm
Amend precepts which are inconsistent with Commission CT1 guidance (30th March 2010) Avoid too much detail in the text in order to make easier the adaptation to EU legislative changes in future Simplification where possible Update precepts on Ethics Committees (Law 14/2007 on biomedical research) Amendment of RD 223/2004 on CT
Where are we going? 2 Operative Changes
EudraCT v8 Update of CT application form Identification of fields to be displayed in the EU CT register CT applications for paediatric CT in third countries (part of a PIP). Multilingual free text fields Update of validation rules Portal ECM Submission of CT applications without electronic signature Possibility of submission of any CT application/notification (except SUSARs and DSUR) Same validation rules as EudraCT v8 (plus CEIC and sites) CTA form should be filled in EudraCT v8.
Key issues for the future New legislation Simplification of procedures Coordination Risk based approach Increase of efficiency Transparency
aecaem@aemps.es Consultations on clinical trials on medicinal products Help! incidensayos@aemps.es Problems/comments on electronic CT submissions through Portal ECM
Thank you very much! aecaem@aemps.es incidensayos@aemps.es www.aemps.es